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Comparison of Inhibitory Effects of 3,5,3'-Triiodothyronine (T₃), Thyroxine (T₄), 3,3,',5-Triiodothyronine (rT₃), and 3,3'-Diiodothyronine (T₂) on Thyrotropin-Releasing Hormone-Induced Release of Thyrotropin in the Rat in vitro^*

INDER J. CHOPRA, HAROLD E. CARLSON and DAVID H. SOLOMON

Departments of Medicine, UCLA Center for the Health Sciences and Wadsworth Veterans Administration Hospital Los Angeles, California 90024

Abstract

In order to compare, in vitro, the TSH suppressive effects of iodothyronines, rat pituitary quarters were first preincubated with T₄, T₃, rT₃, or 3,3'-diiodothyronine (T₂) in Gey and Gey buffer containing 1% bovine serum albumin for 2 h at 37 C and then incubated at 37 C for 1 h with the iodothyronine under study and TRH. TSH released into the medium during incubation was compared to that released by control pituitary fragments, which were not exposed to iodothyronines. All four iodothyronines (T₃, T₄, rT₃, and T₂) were able to significantly inhibit the TRH-induced release of TSH from pituitary fragments in a dose range of 0.015–2.2 µg/ml. However, much larger doses of sodium iodide (1.25 mg/ml) and diiodotyrosine (10 and 30 µg/ml) had no significant effect on the release of TSH. Among T₃, rT₃, and T₄, T₃ was the most potent and rT₃ was the least potent. The relative potency of T₃:T₄:rT₃ appeared to be approximately 100:12:1 when estimated from the lowest doses that caused significant inhibition of TRH-induced release of TSH, and approximately 100:6:0.5 when estimated from the doses that caused 50% inhibition of TSH release; the TSH inhibiting potency of T₂ was similar to that of rT₃. The activity of T₄ could not be explained entirely on the basis of contamination of T₄ with T₃ or by in vitro conversion of T₄ to T₃. Similarly, the available data suggested that rT₃ and T₂ possess some, albeit modest, intrinsic TSH-suppressive activity. TSH-inhibiting activities of T₃, T₄, and rT₃ were also studied using pituitary fragments from starved and iodine-deficient rats. There was no evidence of a change in the sensitivity of the thyrotroph to either T₃ or T₄ in starvation. Similarly, comparison of the responses to several doses of rT₃ did not indicate any significant abnormality in the sensitivity of the thyrotroph to rT₃ in starvation or iodine deficiency. However, comparison of the TSH-suppresive effects of T₄ in the iodine-deficient and normal rat indicated a significant increase in the sensitivity of the thyrotroph to T₄ in iodine deficiency. A similar trend was also evident in the effect of T₃ in iodine deficiency, but it fell short of statistical significance.

Footnotes

^* This work was supported in part by USPHS Grants AM-16155 and AM-17251, and NIH Research Career Development Award 5 K04, AM-70,225 (I.J.C.).

To whom requests for reprints should be addressed.

Received May 23, 1977.

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